Tugba Sismanlar

Genotype alone does not predict the clinical course of SFTPC deficiency in paediatric patients

Patients with interstitial lung disease due to surfactant protein C (SFTPC) mutations are rare and not well characterised. We report on all subjects collected over a 15-year period in the kids-lung register with interstitial lung disease and a proven SFTPC mutation. We analysed clinical courses, interventions and outcomes, as well as histopathological and radiological interrelations. 17 patients (seven male) were followed over a median of 3 years (range 0.3–19). All patients were heterozygous carriers of autosomal dominant SFTPC mutations. Three mutations (p.L101P, p.E191 K and p.E191*) have not been described before in the context of surfactant protein C deficiency. Patients with alterations in the BRICHOS domain of the protein (amino acids 94–197) presented earlier. At follow-up, one patient was healthy (2 years), six patients were “sick-better” (2.8 years, range 0.8–19), seven patients were “sick-same” (6.5 years, 1.3–15.8) and three patients were “sick-worse” (0.3 years, 0.3–16.9). Radiological findings changed from ground-glass to increasing signs of fibrosis and cyst formation with increasing age. Empiric treatments had variable effects, also in patients with the same genotype. Prospective studies with randomised interventions are urgently needed and can best be performed in the framework of international registers. Genotype alone does not predict the clinical course of surfactant protein C deficiency in children and young adults http://ow.ly/GRhCc

Lung disease caused by ABCA3 mutations

Background Knowledge about the clinical spectrum of lung disease caused by variations in the ATP binding cassette subfamily A member 3 (ABCA3) gene is limited. Here we describe genotype-phenotype correlations in a European cohort. Methods We retrospectively analysed baseline and outcome characteristics of 40 patients with two disease-causing ABCA3 mutations collected between 2001 and 2015. Results Of 22 homozygous (15 male) and 18 compound heterozygous patients (3 male), 37 presented with neonatal respiratory distress syndrome as term babies. At follow-up, two major phenotypes are documented: patients with (1) early lethal mutations subdivided into (1a) dying within the first 6 months or (1b) before the age of 5 years, and (2) patients with prolonged survival into childhood, adolescence or adulthood. Patients with null/null mutations predicting complete ABCA3 deficiency died within the 1st weeks to months of life, while those with null/other or other/other mutations had a more variable presentation and outcome. Treatment with exogenous surfactant, systemic steroids, hydroxychloroquine and whole lung lavages had apparent but many times transient effects in individual subjects. Conclusions Overall long-term (>5 years) survival of subjects with two disease-causing ABCA3 mutations was <20%. Response to therapies needs to be ascertained in randomised controlled trials.

Life-threatening, giant pneumatoceles in the course of surfactant protein C deficiency.

Chronic interstitial lung diseases are rare in childhood and can present with a wide spectrum of histological abnormalities and radiological‐clinical phenotypes. A 17‐month‐old female infant with malnutrition, recurrent lower respiratory tract infections, and failure to thrive since 3 months of age was diagnosed as surfactant protein C deficiency. Diffuse, giant, and life‐threatening pneumatoceles developed during the course. They were treated with empiric drug treatment and oxygen support, and resolved rapidly. Substantial clinical and radiological improvement was observed 1 year after treatment initiation. Large‐giant pneumatoceles can develop in the course of surfactant protein C deficiency and may be associated with biopsy. They can resolve with medical treatment. If available, genetic testing should be attempted as a first step for diagnosis. Pediatr Pulmonol. 2015; 50:E25–E28.

Successful embolization in childhood hemoptysis due to abnormal systemic arterial bleeding of the lung and review of the literature

Hemoptysis in children is a rare but potentially life‐threatening symptom of an underlying respiratory tract abnormality. Hemoptysis, when massive and untreated, has a mortality rate of more than 50%. With interventional radiological procedures and surgery, this rate has dropped to 7%–18%. The experience with bronchial arterial embolization in childhood is very limited; only a few case reports with short‐term follow‐up have been reported.

The effect of vitamin D on lower respiratory tract infections in children.

AIM Lower respiratory tract infections including mainly pneumonia represent an important public health problem leading to high mortality and mobidity rates in children aged below five years in developing countries including our country. Vitamin D deficiency has been associated with increased risk of rickets/osteomalacia, various cancers, autoimmune diseases, hyperproliferative skin diseases, cardiovascular system diseases and infectious diseases. Vitamin D has an important role in cellular and humoral immunity and pulmonary functions. Vitamin D deficiency and lower respiratory tract infection are common health problems in children in our country and no clinical study investigating the relationship between these problems has been conducted so far. In this case-control study, we aimed to assess the association between vitamin D level and lower respiratory tract infection in children. MATERIAL AND METHODS Sixty-three children aged between six months and five years with lower respiratory infections and 59 age-matched children who had no history of respiratory symptoms in the last month and no accompanying chronic disease were compared in terms of vitamin D levels. The children in the patient group were also evaluated by the clinical picture. RESULTS No significant correlation was found between vitamin D levels and lower respiratory tract infection in terms of disease and its severity. However, it was found that vitamin D deficiency/ insufficiency was observed with a high rate in all children included in the study. CONCLUSIONS Although no correlation was found between vitamin D level and lower respiratory tract infection, it is recommended that vitamin D level should be measured in children with lower respiratory tract infection and vitamin D supplementation should be given to all children especially in winter months based on the fact that the level of vitamin D was lower than normal in approximately half of the children included in the study and considering the effects of vitamin D on infections, pulmonary functions and immunity.

Respiratory Bronchiolitis–Associated Interstitial Lung Disease in Childhood: New Sequela of Smoking

Childhood interstitial lung diseases are rare disorders of largely unknown etiology characterized by variable types and degrees of parenchymal inflammation. Disease spectrum and prognosis considerably from those in adults. Respiratory bronchiolitis–associated interstitial lung disease (RB-ILD) is a well-described entity occurring almost exclusively in adults who are current heavy cigarette smokers. We describe an 11-year-old boy with failure to thrive, dry cough, and exertional dyspnea for 1 year who was diagnosed with RB-ILD due to heavy passive smoking exposure. Although RB-ILD is well defined in smoking adults, there are no reports in the English literature in nonactive smokers, especially in childhood.

327 Severe anemia in infancy may be the first sign of cystic fibrosis

Objectives Although cystic fibrosis is common, presentation may be atypical. Anemia in CF has been previously described with varying prevalence as high as 33%. To the best knowledge of the authors, there is no data about severe anemia as an initiation sign. Methods Patients with diagnosis as CF were reviewed in terms of anemia and hematologic abnormalities as the initiation sign. Results In 2009–2014, 62 patients were diagnosed as CF in Gazi University Pediatric Pulmonology Department. Hematologic abnormalities were the first symptom in 7 of 62 (11.2%) patients. The mean age was 3.3±1.1 months and 4 (57%) of them were male. None of them had any complaints about the respiratory system in time of diagnosis. Severe anemia (hemoglobin Conclusion Severe anemia may be the first sign of cystic fibrosis especially in infancy. Cystic fibrosis should be included in the differential diagnosis of severe anemia of infancy.

330 Hepatopulmonary syndrome may mask cystic fibrosis

Clinically significant hepatobiliary manifestations of CF are reported to occur in 15–30% of children and cirrhosis is reported in 5–10% of pediatric populations. A 7 year-old boy consultated to pediatric pulmonology clinic with chronic cough, decreased exercise tolerance for six months and cyanosis for 15 days, in terms of hepatopulmonary syndrome. He was under investigation because of hepatosplenomegaly for one year. Physical examination demonstrated tachypnea, mild clubbing, orthodeoxia (saturation 81–82% in the upright position and 86–88% in the supine position) and common crepitan crackles on the auscaltation. On abdominal examination hepatosplenomegaly were present. The calculated alveolar-arterial oxygen gradient was 43 mmHg. Chest x-ray and CT demonstrated dilated peripheral vasculature and bronchiectasis. Liver function tests, coagulation profiles, serum ceruloplasmin, alpha-1 antitrypsin, antinuclear antibodies, anti smooth muscle antibody were all normal. Endoscopy of upper gastrointestinal tract showed no esophageal varices. Liver biopsy findings resulted as cirrhotic liver showing signs of ascending cholangitis. But definitive diagnosis was not determined for one year. Contrast-enhanced echocardography with agitated saline was compatible with intrapulmonary shunting. Although patient denied recurrent lower respiratory tract infection, diarrhea, malnutrition, CF was diagnosed with p.G85E (c.254G>A), p.I148T (c443T>C) mutation. Cystic fibrosis should be investigated in cirrhotic patients with respiratory signs. Hepatosplenomegaly may be the first sign of CF.